The science of NETs is evolving rapidly

Bridging the knowledge gap in this challenging disease state requires a concerted effort from the healthcare community.

Research involving NETs is ongoing
Currently, there are over 1,000 trials in various stages of activity registered with the U.S. National Institutes of Health1

  • One example of topics being explored is the influence of various pathways on gene transcription and cell cycle progression 2

Basic and clinical medical research continue to improve our understanding of the biology and clinical behavior of NETs.2,3 While much work remains to be done, it is likely that the appearance and growth of NETs involve a series of genetic alterations leading to the activation of oncogenes, and/or inactivation of tumor suppressor genes, and the resultant failure of apoptosis.3

The cellular proteins and receptors that may be implicated in these processes include vascular endothelial growth factor (VEGF) and its receptors (VEGFR1-3), epidermal growth factor receptor (EGFR), insulin growth factor-I receptor (IGF-IR), and the phosphoinositol-3-kinase (PI3K)–phosphatase and tensin homolog deleted (PTEN)–AKT–mammalian target of rapamycin (mTOR) pathway.2

A related area of interest is in building regional and national databases and tissue banks to identify molecular prognostic factors for NETs. This information may help us better understand the natural history of NETs and identify high-risk patients.3,4

A need for new biomarkers

Another key research focus is on the identification and validation of new NET biomarkers.

A number of biomarkers currently are used in the diagnosis and management of NETs. These include general tumor markers, such as CgA and neuron-specific enolase (NSE), and specific tests for measuring hormones. Although these biomarkers are useful, they all have limitations and their results should be supplemented with imaging and/or endoscopic techniques and biopsy.5,6 Some biomarkers are not sensitive or specific enough to provide clinically useful diagnostic and prognostic information.7 Others appear promising but have not yet been validated in large clinical trials.8

Overall, new biomarkers are needed that can more reliably and cost-effectively be used to screen populations at risk for developing NETs, and assess the potential aggressiveness of a patient's tumor.8,9

Expert Point of View

Watch videos and read insights from leading physicians about best practices for managing patients with NETs.

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A Multidisciplinary Approach

Multidisciplinary Approach

"...the many treatments that are out there...really involve more than one decision by one specialty. It really involves
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1. U.S. National Institutes of Health. Clinical Trials.gov
http://www.clinicaltrials.gov/ct2/results?flds=Xn&flds=a&flds=b&term=Neuroendocrine+
Tumors&show_flds=Y. Accessed September 20, 2011.
2. Capdevila J, Salazar R. Molecular targeted therapies in the treatment of gastroenteropancreatic neuroendocrine tumors. Targ Oncol. 2009;4(4):287-296.
3. Barakat MT, Meeran K, Bloom SR. Neuroendocrine tumours. Endocr Relat Cancer. 2004;11(1):1-18.
4. Modlin IM, Moss SF, Chung DC, Jensen RT, Snyderwine E. Priorities for improving the management of gastroenteropancreatic neuroendocrine tumors. J Natl Cancer Inst. 2008;100:1282-1289.
5. Modlin IM, Latich I, Zikusoka M, Kidd M, Eick G, Chan AKC. Gastrointestinal carcinoids: the evolution of diagnostic strategies. J Clin Gastroenterol. 2006;40(7):572-582.
6. Mamikunian G, Vinik AI, O'Dorisio TM, Woltering EA, Go VLW. Diagnosing and treating gastroenteropancreatic tumors, including ICD-9 codes. In: Neuroendocrine Tumors: A Comprehensive Guide to Diagnosis and Management. 4th ed. Inglewood, CA: Inter Science Institute; 2009:1-43.
7. Foster CS, Cooper CS. Urgent need to develop independent biomarkers for functional, diagnostic and prognostic application in oncology research. Biomarkers Med. 2009;3(4):329-333.
8. Hewitt SM, Takikita M, Braunschweig T, Chung J-Y. Promises and challenges of predictive tissue biomarkers. Biomarkers Med. 2007;1(2):313-318.
9. Urtishak S, Alpaugh RK, Weiner LM, Swaby RF. Clinical utility of circulating tumor cells: a role for monitoring response to therapy and drug development. Biomarkers Med. 2008;2(2):137-145.